Melanocortin receptors have a role in appetite control and sexual function. Main interest seems to be in the Melanocortin receptors 3 and 4, though 4 is mostly identified to be involved in those functions. Melanocortin receptor 4 in turn is modulated via 5-HT2C and 5-HT1B to reduce appetite and apparently increase erection and sexual behaviour.
5-HT-mediated appetite through the engagement of the ARC melanocortin system occurs via a three-pronged mechanism: (1) direct activation of anorectic pro-opiomelanocortin (POMC) neurons (the endogenous melanocortin receptor agonist) via 5-HT2CRs, (2) indirect 5-HT1BR-mediated disinhibition of anorectic POMC neurons via suppression of local inhibitory inputs
There is abundant expression of both MC3R and MC4R in the brain and in peripheral genital sensory outputs (Figure 2).27 However, MC4R has been shown to modulate erectile function and sexual behavior, whereas MC3R has not been shown to have a pro-erectile effect.